Responses to Influenza Vaccine in Patients With Mitochondrial Disorders (MELAS)

MELAS Syndrome Clinical Trial

Official title:

Metabolic and Immune Responses to TIV in Patients With Mitochondrial Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01831934
• Other study ID #: SU-18615
• Secondary ID: R21HD061709-01A1
• Status: Completed
• Phase: Phase 4
• First received: March 19, 2013
• Last updated: May 7, 2014
• Start date: September 2010
• Est. completion date: March 2012

Study information

• Verified date: May 2014
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This pilot clinical study, funded by the National Institutes of Health, will evaluate the safety and metabolic responses to a licensed inactivated seasonal influenza vaccine (TIV). This single arm study will consist of two cohorts: MELAS syndrome volunteers (a specific identified disorder of mitochondrial dysfunction: mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) between 13-60 years for OR adult control volunteers between 18-65 years of age. Both cohorts will receive the same treatment: a single vaccination with an FDA-licensed intramuscular seasonal trivalent inactivated influenza vaccine (TIV).

Description:

Mitochondrial disease constitutes the most common neurometabolic disease of childhood with an estimated minimal lifetime risk of developing this disorder of 1 in 5000 live births.

This pilot study will for the first time prospectively assess the safety of seasonal flu immunization in a subgroup of patients with MELAS syndrome. Comparing their responses to those of healthy young control volunteers will provide new information about the safety and immunogenicity of flu vaccination in this important sub-population and help guide the design of future studies that can be carried out in younger children.

All participants will receive a single administration of a licensed influenza vaccine. Prior to vaccination, participants will provide information regarding health history and responses to health questionnaires. Vital signs will be assessed. A blood sample and urine specimen will be collected prior to vaccination, and at 6 hours, 5-7 days and 26-30 days post-immunization. Volunteers will be asked to keep a diary of symptoms post-vaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: March 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 13 Years to 65 Years

Eligibility

Inclusion Criteria:Inclusion criteria include:

• Age between 13-60 years for MELAS volunteers OR age between 18-65 years for adult control volunteers. Control volunteers will be age-matched +/-5 years to enrolled MELAS volunteers. If the MELAS volunteer has diabetes and uses insulin daily, their control will be an adult with diabetes who uses insulin daily.

• General good health at time of enrollment

• Willing and able to sign Informed Consent

• Available for follow-up for the planned duration of the study

• Acceptable medical history by screening evaluation and brief clinical assessment

• All female participants of childbearing potential must use an acceptable method of contraception and not become pregnant for the duration of the clinical phase of the study (approximately 1 month to completion of Visit 4). (Acceptable contraception may include but is not limited to implants, injectables, combined oral contraceptives, effective intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner).

Exclusion Criteria:Exclusion criteria will include:

• Allergy to egg or egg products or allergy to vaccine components, including thimerosal

• Active systemic or serious concurrent illness, including febrile illness, within the 3 days prior to study vaccination

• History of immunodeficiency, known or suspected impairment of immunologic function, including, but not limited to, clinically significant liver disease, moderate to severe renal disease, or any other chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.

• Blood pressure >150 systolic or >95 diastolic at Visit 1.

• Hospitalization in the past year for congestive heart failure or emphysema.

• History of chronic Hepatitis B or C.

• Recent or current use of immunosuppressive medication, including glucocorticoids (corticosteroid nasal sprays are permissible).

• Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors such as breast cancer or prostate cancer with recurrence in the past year, and any hematologic cancer such as leukemia).

• Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.

• History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year

• Receipt of blood or blood products within the past 6 months

• Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol

• Inactivated vaccine 14 days prior to vaccination or live, attenuated vaccine within 60 days of vaccination

• History of Guillain-Barré Syndrome

• Pregnant or lactating woman

• Use of investigational agents within 30 days prior to enrollment

• Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment

• Any condition which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• MELAS Syndrome
• Mitochondrial Diseases

Intervention

Biological:
• Intramuscular seasonal trivalent inactivated influenza vaccine
FDA-licensed seasonal influenza vaccine

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical safety of TIV vaccine	We will measure solicited local and systemic adverse events and SAEs for 1 month following immunization	Day 0 to Day28	Yes
Secondary	Measurement of intracellular ROS and RNS by Hi-D FACS	Intracellular ROS (iROS) will be measured by established protocols using the fluorescent dye DHR123 (Dihydrorhodamine 123).; Intracellular RNS (iRNS) will be measured by established protocols using the fluorescent dye DAF-FM, DA (4-amino-5methylamino-2',7'-difluorofluorescein, diacetate)	Day 0 to Day 28	Yes
Secondary	Measurement of intracellular glutathione by Hi-D FACS (CD4 and CD8 T cells) and tandem mass spectrometry (whole blood)	This method relies on the ability of intracellular glutathione S-transferases to tag GSH to bimane to yield a bimane-GS conjugate that fluoresces at 440 nm.	Day 0-Day 28	Yes
Secondary	Comprehensive immune response profile to influenza	We will conduct a comprehensive analysis of serum cytokines, white blood cell subsets, gene expression and influenza-specific antibody and T cell responses in patients with mitochondrial dysfunction vs. controls	Day 0 to Day 28	No

External Links

•   Stanford-LPCH Vaccine Program website for clinical trials
•   United Mitochondrial Disease Foundation website